German Henostroza

ABSTRACT The characteristics of loop-mediated isothermal amplification (LAMP) make it a promising platform for the molecular detection of tuberculosis (TB) in developing countries. Here, we report on the first clinical evaluation of LAMP for the detection of pulmonary TB in microscopy centers in Peru, Bangladesh, and Tanzania to determine its operational applicability in such settings. A prototype LAMP assay with simplified manual DNA extraction was evaluated for accuracy and ease of use. The sensitivity of LAMP in smear- and culture-positive sputum specimens was 97.7% (173/177 specimens; 95% confidence interval [CI], 95.5 to 99.9%), and the sensitivity in smear-negative, culture-positive specimens was 48.8% (21/43 specimens; CI, 33.9 to 63.7%). The specificity in culture-negative samples was 99% (500/505 specimens; CI, 98.1 to 99.9%). The average hands-on time for testing six samples and two controls was 54 min, similar to that of sputum smear microscopy. The optimal amplification time was 40 min. No indeterminate results were reported, and the interreader variability was 0.4%. Despite the use of a single room without biosafety cabinets for all procedures, no DNA contamination was observed. The assay was robust, with high end-point stability and low rates of test failure. Technicians with no prior molecular experience easily performed the assay after 1 week of training, and opportunities for further simplification of the assay were identified.

A vaccine to interrupt the transmission of tuberculosis is needed.We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both.We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups.M72/AS01E provided 54.0% protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .).

Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings.We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per μL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 2·5 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080.Between Oct 31, 2011, and June 9, 2014, we enrolled 850 participants. Of these, we randomly assigned 424 to receive empirical tuberculosis therapy and 426 to the isoniazid preventive therapy group. The median CD4 cell count at baseline was 18 cells per μL (IQR 9-32). At week 24, 22 (5%) participants from each group died or were of unknown status (95% CI 3·5-7·8) for empirical group and for isoniazid preventive therapy (95% CI 3·4-7·8); absolute risk difference of -0·06% (95% CI -3·05 to 2·94). Grade 3 or 4 signs or symptoms occurred in 50 (12%) participants in the empirical group and 46 (11%) participants in the isoniazid preventive therapy group. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) participants in the empirical group and 97 (23%) participants in the isoniazid preventive therapy group.Empirical tuberculosis therapy did not reduce mortality at 24 weeks compared with isoniazid preventive therapy in outpatient adults with advanced HIV disease initiating antiretroviral therapy. The low mortality rate of the trial supports implementation of systematic tuberculosis screening and isoniazid preventive therapy in outpatients with advanced HIV disease.National Institutes of Allergy and Infectious Diseases through the AIDS Clinical Trials Group.

Background Tuberculosis (TB) and human immunodeficiency virus (HIV) represent two of the greatest health threats in African prisons. In 2010, collaboration between the Centre for Infectious Disease Research in Zambia, the Zambia Prisons Service, and the National TB Program established a TB and HIV screening program in six Zambian prisons. We report data on the prevalence of TB and HIV in one of the largest facilities: Lusaka Central Prison. Methods Between November 2010 and April 2011, we assessed the prevalence of TB and HIV amongst inmates entering, residing, and exiting the prison, as well as in the surrounding community. The screening protocol included complete history and physical exam, digital radiography, opt-out HIV counseling and testing, sputum smear and culture. A TB case was defined as either bacteriologically confirmed or clinically diagnosed. Results A total of 2323 participants completed screening. A majority (88%) were male, median age 31 years and body mass index 21.9. TB symptoms were found in 1430 (62%). TB was diagnosed in 176 (7.6%) individuals and 52 people were already on TB treatment at time of screening. TB was bacteriologically confirmed in 88 cases (3.8%) and clinically diagnosed in 88 cases (3.8%). Confirmed TB at entry and exit interventions were 4.6% and 5.3% respectively. Smear was positive in only 25% (n = 22) of bacteriologically confirmed cases. HIV prevalence among inmates currently residing in prison was 27.4%. Conclusion Ineffective TB and HIV screening programs deter successful disease control strategies in prison facilities and their surrounding communities. We found rates of TB and HIV in Lusaka Central Prison that are substantially higher than the Zambian average, with a trend towards concentration and potential transmission of both diseases within the facility and to the general population. Investment in institutional and criminal justice reform as well as prison-specific health systems is urgently required.

Tuberculosis is one of the fastest-growing epidemics in prison populations in sub-Saharan Africa (SSA), constituting a threat to both inmates and the wider community. Various factors have contributed to the breakdown of tuberculosis control in prison facilities in SSA, including slow and insensitive diagnostics, failing prison infrastructure, inadequate funding, and weak prevention and treatment interventions for human immunodeficiency virus (HIV). In this article, we describe the challenges inherent in current approaches to tuberculosis control in prisons and consider the alternatives. We argue that although improved implementation of conventional tuberculosis control activities is necessary, considerable investment in a broader range of public health interventions, including infrastructure and staffing upgrades, cutting-edge tuberculosis diagnostics, and combination prevention for HIV, will be equally critical. This combination response to tuberculosis in prisons will be essential for tackling existing and nascent prison tuberculosis epidemics and will require high-level political support and financing.

Objective To improve the Zambia Prisons Service's implementation of tuberculosis screening and human immunodeficiency virus (HIV) testing.Methods For both tuberculosis and HIV, we implemented mass screening of inmates and community-based screening of those residing in encampments adjacent to prisons.We also established routine systems -with inmates as peer educators -for the screening of newly entered or symptomatic inmates.We improved infection control measures, increased diagnostic capacity and promoted awareness of tuberculosis in Zambia's prisons.Findings In a period of 9 months, we screened 7638 individuals and diagnosed 409 new patients with tuberculosis.We tested 4879 individuals for HIV and diagnosed 564 cases of infection.An additional 625 individuals had previously been found to be HIV-positive.Including those already on tuberculosis treatment at the time of screening, the prevalence of tuberculosis recorded in the prisons and adjacent encampments -6.4% (6428/100 000) -is 18 times the national prevalence estimate of 0.35%.Overall, 22.9% of the inmates and 13.8% of the encampment residents were HIV-positive.Conclusion Both tuberculosis and HIV infection are common within Zambian prisons.We enhanced tuberculosis screening and improved the detection of tuberculosis and HIV in this setting.Our observations should be useful in the development of prison-based programmes for tuberculosis and HIV elsewhere.

Background Prison populations in sub-Saharan Africa (SSA) experience a high burden of disease and poor access to health care. Although it is generally understood that environmental conditions are dire and contribute to disease spread, evidence of how environmental conditions interact with facility-level social and institutional factors is lacking. This study aimed to unpack the nature of interactions and their influence on health and healthcare access in the Zambian prison setting. Methods We conducted in-depth interviews of a clustered random sample of 79 male prisoners across four prisons, as well as 32 prison officers, policy makers and health care workers. Largely inductive thematic analysis was guided by the concepts of dynamic interaction and emergent behaviour, drawn from the theory of complex adaptive systems. Results A majority of inmates, as well as facility-based officers reported anxiety linked to overcrowding, sanitation, infectious disease transmission, nutrition and coercion. Due in part to differential wealth of inmates and their support networks on entering prison, and in part to the accumulation of authority and material wealth within prison, we found enormous inequity in the standard of living among prisoners at each site. In the context of such inequities, failure of the Zambian prison system to provide basic necessities (including adequate and appropriate forms of nutrition, or access to quality health care) contributed to high rates of inmate-led and officer-led coercion with direct implications for health and access to healthcare. Conclusions This systems-oriented analysis provides a more comprehensive picture of the way resource shortages and human interactions within Zambian prisons interact and affect inmate and officer health. While not a panacea, our findings highlight some strategic entry-points for important upstream and downstream reforms including urgent improvement in the availability of human resources for health; strengthening of facility-based health services systems and more comprehensive pre-service health education for prison officers.

Resistance to commonly used antituberculosis drugs is emerging worldwide. Conventional drug-susceptibility testing (DST) methods are slow and demanding. Alternative, rapid DST methods would permit the early detection of drug resistance and, in turn, arrest tuberculosis transmission.A cost-effectiveness analysis of 5 DST methods was performed in the context of a clinical trial that compared rapid with conventional DST methods. The methods under investigation were direct phage-replication assay (FASTPlaque-Response; Biotech), direct amplification and reverse hybridization of the rpoB gene (INNO-LiPA; Innogenetics), indirect colorimetric minimum inhibitory concentration assay (MTT; ICN Biomedicals), and direct proportion method on Löwenstein-Jensen medium. These were compared with the widely used indirect proportion method on Löwenstein-Jensen medium.All alternative DST methods were found to be cost-effective, compared with other health care interventions. DST methods also generate substantial cost savings in settings of high prevalence of multidrug-resistant tuberculosis. Excluding the effects of transmission, the direct proportion method on Löwenstein-Jensen medium was the most cost-effective alternative DST method for patient groups with prevalences of multidrug-resistant tuberculosis of 2%, 5%, 20%, and 50% (cost in US$2004, $94, $36, $8, and $2 per disability-adjusted life year, respectively).Alternative, rapid methods for DST are cost-effective and should be considered for use by national tuberculosis programs in middle-income countries.

Background: Whereas access to antiretroviral therapy (ART) for HIV-infected individuals in the developing world is increasing, data on factors impacting initial regimen durability are lacking. Methods: Retrospective review patients starting initial ART at Instituto de Medicine Tropical (Lima, Peru) April 1, 2004 to December 30, 2007. Survival methods (Kaplan-Meier, Cox proportional hazard) assessed factors associated with regimen durability including an interaction term between nucleoside reverse transcriptase inhibitor backbone and time. Results: Decreased initial regimen durability was observed with weight <60 kg [hazards ratio (HR) = 1.77; 95% confidence interval (CI) = 1.25-2.51], CD4 <200 (HR = 1.73; 95% CI = 1.03-2.91), and zidovudine (AZT) use at <120 days (HR = 2.09; 95% CI = 1.22-3.57). In contrast, after 120 days, AZT use decreased risk of discontinuation (HR = 0.52; 95% CI = 0.28-0.95). Early (<120 days) toxicity-related discontinuation of AZT containing regimens was observed in 44% of patients <50 kg at baseline vs. 14% of those >70 kg. An increased risk of early toxicity-related discontinuation of AZT-containing regimens was observed for baseline weight <60 kg (HR = 2.52; 95% CI = 1.46-4.35). Conclusions: Lower baseline weight and lower CD4 values at ART initiation were associated with decreased regimen durability. Compared with didanosine/stavudine, AZT use initially increased, then subsequently (>120 days) lowered hazards for regimen discontinuation. Weight <60 kg was associated with an increased risk of toxicity-related AZT discontinuation. As ART use expands globally, further study into maximally durable, least toxic regimens, and the role of weight-based AZT dosing is imperative.

To determine the incidence of and risk factors for surgical-site infections (SSIs) after abdominal surgery.A cohort study was conducted from January to June 1998. CDC criteria for SSI and the NNIS System risk index were used.A tertiary-care hospital in Peru.Adult patients undergoing abdominal surgery who consented were enrolled and observed until 30 days after surgery. Patients who had undergone surgery at another hospital or who died or were transferred to another hospital within 24 hours after surgery were excluded.Four hundred sixty-eight patients were enrolled. Their mean age was 37.2 years. One hundred twenty-five patients developed SSIs, 18% of which were identified after discharge. The overall incidence rate (IR) was 26.7%. The IR was 13.9% for clean, 15.9% for clean-contaminated, 13.5% for contaminated, and 47.2% for dirty interventions. The IR was 3.6% for NNIS System risk index 0 and 60% for index 3. Risk factors for SSI on logistic regression analysis were dirty or infected wound (RR, 3.8; CI95, 1.7-8.4), drain use longer than 9 days (RR, 6.0; CI95, 2.5-12.5), and length of surgery greater than the 75th percentile (RR, 2.1; CI95, 1.0-4.4). Patients with SSI had a longer hospital stay than did non-infected patients (14.0 vs 6.1 days; p < .001).SSI is a major problem in this hospital, which has a higher IR (especially for clean interventions) than those of developed countries. In developing countries, prevention of SSI should include active surveillance and interventions targeting modifiable risk factors.

Tuberculosis (TB) and human T-lymphotropic virus 1 (HTLV-1) are frequent in Peru. The prevalence of HTLV-1 among Peruvian TB patients is unknown.To determine the prevalence of HTLV-1, HTLV-2 and the human immunodeficiency virus (HIV) in out-patients with TB and to compare HTLV-1-infected patients with seronegative patients.Cross-sectional study including subjects aged 18-65 years diagnosed with smear-positive pulmonary TB at health centres in northern Lima from November 2004 to August 2005. HTLV and HIV screening was performed using enzyme-linked immunosorbent assay; HTLV-1 and HTLV-2 were confirmed using line immunoassay.There were 311 participants with a median age of 29 years; 173 (56%) were men. HTLV-1 prevalence was 5.8% (18/311, 95%CI 3.2-8.4) and HIV prevalence was 1.3% (4/304, 95%CI 0.4-3.3). HTLV-2 was not diagnosed. In comparison with HIV- and HTLV-seronegative patients, HTLV-1-infected subjects were older (median age 44 vs. 28, P < 0.001) and were more likely to have been born in the southern Andes (OR 4.4, 95%CI 1.6-11.9). They were also more likely to report a history of TB deaths in the family (OR 5.4, 95%CI 1.7-16.8) and had more sputum smear results graded as 3+ (OR 4.1, 95%CI 1.5-11.2).HTLV-1 screening among Peruvian TB patients is important. Because 3+ sputum smears are frequent and mortality is high among relatives, families of HTLV-1/TB-positive cases merit special attention.

Reactive case detection (RACD) for malaria is a strategy that may be used to complement passive surveillance, as passive surveillance fails to identify infections that are asymptomatic or do not seek care. The spatial and seasonal patterns of incident (index) cases reported at a single clinic in Chongwe District were explored. A RACD strategy was implemented from June 2012 to June 2013 in a single catchment area in Chongwe District. Incident (index) cases recorded at the clinic were followed up at their household, and all household contacts were tested for malaria using rapid diagnostic tests (RDTs). GPS coordinates were taken at each index household. Spatial analyses were conducted to assess characteristics related to clustering, cluster detection and spatial variation in risk of index houses. Effects of season (rainy versus dry), distance to the clinic and distance to the main road were considered as modifying factors. Lastly, logistic regression was used to identify factors associated with the proportion of household contacts testing RDT positive. A total of 426 index households were enrolled, with 1,621 household contacts (45% RDT positive). Two space–time clusters were identified in the rainy season, with ten times and six times higher risk than expected. Significantly increased spatial clustering of index households was found in the rainy season as compared to the dry season (based on K-function methodology). However, no seasonal difference in mapped spatial intensity of index households was identified. Logistic regression analysis identified two main factors associated with a higher proportion of RDT positive household contacts. There was a 41% increased odds of RDT positive household contacts in households where the index case was under 5 years of age [OR = 1.41, 95% confidence intervals (1.15, 1.73)]. For every 500-m increase in distance from the road, there was a 5% increased odds of RDT positive household contacts [OR = 1.05 (1.02, 1.07)], controlling for season. Areas of increased report of malaria persist after controlling for distance to the clinic and main road. Clinic-based interventions will miss asymptomatic, non-care seeking infections located farther from the road. RACD may identify additional infections missed at the clinic.

Tuberculosis (TB) remains a leading cause of morbidity and mortality in sub-Saharan Africa. In Zambia, smear microscopy and chest radiography (CXR) are the primary TB diagnostic tools, and most cases are not bacteriologically confirmed.We implemented enhanced screening to determine the TB burden among new human immunodeficiency virus (HIV) clinic enrollees.Consecutive adult HIV clinic enrollees were screened, regardless of symptoms. All underwent microscopy (Ziehl-Neelsen/fluorescence microscopy) on three sputum specimens, physical examination, and digital CXR. Sputum, blood and urine specimens were cultured. Xpert(®) MTB/RIF testing was performed retrospectively.From July 2011 to April 2012, 399 patients were enrolled. The median age was 34.4 years; body mass index was 20.8 kg/m(2), CD4 count was 202 cells/μl and 86% were symptomatic. Culture-confirmed TB was diagnosed in 72/399 (18%) patients; an additional 31/399 (8%) were culture-negative but diagnosed clinically. Symptom screening for any cough, fever, weight loss or night sweats had high sensitivity (95%) but low specificity (14%) for detecting culture-confirmed cases. Among culture-confirmed cases, 35/72 (49%) were missed clinically and detected only by culture. Xpert was 64% sensitive and 98% specific.High TB prevalence was found in Zambians newly enrolled into HIV care. Screening with sensitive diagnostics should be considered with culture when feasible in this population.

Health and health service access in Zambian prisons are in a state of ‘chronic emergency’. This study aimed to identify major structural barriers to strengthening the prison health systems. A case-based analysis drew on key informant interviews (n = 7), memos generated during workshops (n = 4) document review and investigator experience. Structural determinants were defined as national or macro-level contextual and material factors directly or indirectly influencing prison health services. The analysis revealed that despite an favourable legal framework, four major and intersecting structural factors undermined the Zambian prison health system. Lack of health financing was a central and underlying challenge. Weak health governance due to an undermanned prisons health directorate impeded planning, inter-sectoral coordination, and recruitment and retention of human resources for health. Outdated prison infrastructure simultaneously contributed to high rates of preventable disease related to overcrowding and lack of basic hygiene. These findings flag the need for policy and administrative reform to establish strong mechanisms for domestic prison health financing and enable proactive prison health governance, planning and coordination.

Abstract Objectives To investigate the incidence of selected opportunistic infections ( OI s) and cancers and the role of a history of tuberculosis ( TB ) as a risk factor for developing these conditions in HIV ‐infected patients starting antiretroviral treatment ( ART ) in Southern Africa. Methods Five ART programmes from Zimbabwe, Zambia and South Africa participated. Outcomes were extrapulmonary cryptococcal disease (CM), pneumonia due to Pneumocystis jirovecii (PCP), Kaposi's sarcoma and Non‐Hodgkin lymphoma. A history of TB was defined as a TB diagnosis before or at the start of ART. We used Cox models adjusted for age, sex, CD4 cell count at ART start and treatment site, presenting results as adjusted hazard ratios ( aHR ) with 95% confidence intervals (CI). Results We analysed data from 175 212 patients enrolled between 2000 and 2010 and identified 702 patients with incident CM (including 205 with a TB history) and 487 with incident PCP (including 179 with a TB history). The incidence per 100 person‐years over the first year of ART was 0.48 (95% CI 0.44–0.52) for CM, 0.35 (95% CI 0.32–0.38) for PCP, 0.31 (95% CI 0.29–0.35) for Kaposi's sarcoma and 0.02 (95% CI 0.01–0.03) for Non‐Hodgkin lymphoma. A history of TB was associated with cryptococcal disease ( aHR 1.28, 95% CI 1.05–1.55) and Pneumocystis jirovecii pneumonia ( aHR 1.61, 95% CI 1.27–2.04), but not with Non‐Hodgkin lymphoma ( aHR 1.09, 95% CI 0.45–2.65) or Kaposi's sarcoma ( aHR 1.02, 95% CI 0.81–1.27). Conclusions Our study suggests that there may be interactions between different OI s in HIV ‐infected patients.

Timely diagnosis and treatment of maternal tuberculosis (TB) is important to reduce morbidity and mortality for both the mother and child, particularly in women who are coinfected with HIV. The World Health Organization (WHO) recommends the integration of TB/HIV screening into antenatal services but available diagnostic tools are slow and insensitive, resulting in delays in treatment initiation. Recently the WHO endorsed Xpert MTB/RIF, a highly sensitive, real-time PCR assay for Mycobacterium tuberculosis that simultaneously detects rifampicin resistance directly from sputum and provides results within 100 minutes. We propose a model for same-day TB screening and diagnosis of all pregnant women at antenatal care using Xpert MTB/RIF. Pilot studies are urgently required to evaluate strategies for the integration of TB screening into antenatal clinics using new diagnostic technologies.

Research exploring the drivers of health outcomes of women who are in prison in low- and middle-income settings is largely absent. This study aimed to identify and examine the interaction between structural, organisational and relational factors influencing Zambian women prisoners' health and healthcare access. We conducted in-depth interviews of 23 female prisoners across four prisons, as well as 21 prison officers and health care workers. The prisoners were selected in a multi-stage sampling design with a purposive selection of prisons followed by a random sampling of cells and of female inmates within cells. Largely inductive thematic analysis was guided by the concepts of dynamic interaction and emergent behaviour, drawn from the theory of complex adaptive systems. We identified compounding and generally negative effects on health and access to healthcare from three factors: i) systemic health resource shortfalls, ii) an implicit prioritization of male prisoners' health needs, and iii) chronic and unchecked patterns of both officer- and inmate-led victimisation. Specifically, women's access to health services was shaped by the interactions between lack of in-house clinics, privileged male prisoner access to limited transport options, and weak responsiveness by female officers to prisoner requests for healthcare. Further intensifying these interactions were prisoners' differential wealth and access to family support, and appointments of senior 'special stage' prisoners which enabled chronic victimisation of less wealthy or less powerful individuals. This systems-oriented analysis revealed how Zambian women's prisoners' health and access to healthcare is influenced by weak resourcing for prisoner health, administrative biases, and a prevailing organisational and inmate culture. Findings highlight the urgent need for investment in structural improvements in health service availability but also interventions to reform the organisational culture which shapes officers' understanding and responsiveness to women prisoners' health needs.

Peru reports among the highest multidrug-resistant tuberculosis (MDR-TB) rates in the Americas, with a growing proportion in previously untreated tuberculosis (TB) cases. The identification of clusters of primary MDR-TB compared with drug-susceptible TB (DS-TB) could help prioritize interventions.To examine the clustering of primary MDR-TB case residences and their proximity to high-risk locations in San Juan de Lurigancho District, Lima, Peru.Enrolled primary MDR-TB and primary DS-TB cases were interviewed and their primary residence was recorded using handheld Global Positioning System devices. Kuldorff's spatial scan statistic was used for cluster detection (SaTScan(TM), v. 9.1.1). Identified clusters were visualized in Quantum Geographic Information Systems software (v1.8.0). The following cluster centers were tested: a health centre with the highest TB and MDR-TB rates (Clinic X), a hospital and two prisons. Using regression analyses, we examined predictors of primary MDR-TB cases.A statistically significant cluster of primary MDR-TB cases was identified within a 2.29 km radius around Clinic X. Proximity to Clinic X remained a significant predictor of primary MDR-TB in adjusted regression analyses.We identified a hotspot of primary MDR-TB cases around Clinic X in a TB-endemic area. Causes of this clustering require investigation; targeted interventions for this high-risk area should be considered.

Three out-patient antenatal care (ANC) clinics in Lusaka, Zambia.To estimate tuberculosis (TB) prevalence in human immunodeficiency virus (HIV) infected and symptomatic, non-HIV-infected pregnant women and explore the feasibility of routine TB screening in ANC settings.Peer educators administered TB symptom questionnaires to pregnant women attending their first ANC clinic visit. Presumptive TB patients were defined as all HIV-infected women and symptomatic non-HIV-infected women. Sputum samples were tested using smear microscopy and culture to estimate TB prevalence.All 5033 (100%) women invited to participate in the study agreed, and 17% reported one or more TB symptoms. Among 1152 presumed TB patients, 17 (1.5%) had previously undiagnosed culture-confirmed TB; 2 (12%) were smear-positive. Stratified by HIV status, TB prevalence was 10/664 (1.5%, 95%CI 0. 7-2.8) among HIV-infected women and 7/488 (1.4%, 95%CI 0.6-2.9) among symptomatic non-HIV-infected women. In HIV-infected women, the only symptom significantly associated with TB was productive cough; symptom screening was only 50% sensitive.There is a sizable burden of TB in pregnant women in Zambia, which may lead to adverse maternal and infant outcomes. TB screening in ANC settings in Zambia is acceptable and feasible. More sensitive diagnostics are needed.

Lusaka Central Prison, Zambia.To derive screening rules for tuberculosis (TB) using data collected during a prison-wide TB and human immunodeficiency virus (HIV) screening program.We derived rules with two methodologies: logistic regression and classification and regression trees (C&RT). We evaluated the performance of the derived rules as well as existing World Health Organization (WHO) screening recommendations in our cohort of inmates, as measured by sensitivity, specificity, and positive and negative predictive values.The C&RT-derived rule recommended diagnostic testing of all inmates who were underweight (defined as body mass index [BMI] < 18.5 kg/m(2)] or HIV-infected; the C&RT-derived rule had 60% sensitivity and 71% specificity. The logistic regression-derived rule recommended diagnostic testing of inmates who were underweight, HIV-infected or had chest pain; the logistic regression-derived rule had 74% sensitivity and 57% specificity. Two of the WHO recommendations had sensitivities that were similar to our logistic regression rule but had poorer specificities, resulting in a greater testing burden.Low BMI and HIV infection were the most robust predictors of TB in our inmates; chest pain was additionally retained in one model. BMI and HIV should be further evaluated as the basis for TB screening rules for inmates, with modification as needed to improve the performance of the rules.

Abstract Objectives Prisons act as infectious disease reservoirs. We aimed to explore the challenges of TB control and continuity of care in prisons in Zambia. Methods We evaluated treatment outcomes for a cohort of inmates diagnosed with TB during a TB REACH funded screening programme initiated by the Zambia Prisons Service and the Centre for Infectious Disease Research in Zambia. Results Between October 2010 and September 2011, 6282 inmates from six prisons were screened for TB , of whom 374 (6.0%) were diagnosed. TB treatment was initiated in 345 of 374 (92%) inmates. Of those, 66% were cured or completed treatment, 5% died and 29% were lost to follow‐up. Among those lost to follow‐up, 11% were released into the community and 13% were transferred to other prisons. Conclusions Weak health systems within the Zambian prison service currently undermines continuity of care, despite intensive TB screening and case‐finding interventions. To prevent TB transmission and the development of drug resistance, we need sufficient numbers of competent staff for health care, reliable health information systems including electronic record keeping for prison facilities, and standard operating procedures to guide surveillance, case‐finding and timely treatment initiation and completion.

Background Multidrug-resistant tuberculosis (MDR-TB), resistance to at least isoniazid and rifampin, is a worldwide problem. Objective To develop a clinical prediction rule to stratify risk for MDR-TB among patients with pulmonary tuberculosis. Methods Derivation and internal validation of the rule among adult patients prospectively recruited from 37 health centers (Perú), either a) presenting with a positive acid-fast bacillus smear, or b) had failed therapy or had a relapse within the first 12 months. Results Among 964 patients, 82 had MDR-TB (prevalence, 8.5%). Variables included were MDR-TB contact within the family, previous tuberculosis, cavitary radiologic pattern, and abnormal lung exam. The area under the receiver-operating curve (AUROC) was 0.76. Selecting a cut-off score of one or greater resulted in a sensitivity of 72.6%, specificity of 62.8%, likelihood ratio (LR) positive of 1.95, and LR negative of 0.44. Similarly, selecting a cut-off score of two or greater resulted in a sensitivity of 60.8%, specificity of 87.5%, LR positive of 4.85, and LR negative of 0.45. Finally, selecting a cut-off score of three or greater resulted in a sensitivity of 45.1%, specificity of 95.3%, LR positive of 9.56, and LR negative of 0.58. Conclusion A simple clinical prediction rule at presentation can stratify risk for MDR-TB. If further validated, the rule could be used for management decisions in resource-limited areas.

In Zambia the vast majority of chest radiographs (CXR) are read by clinical officers who have limited training and varied interpretation experience, meaning lower inter-rater reliability and limiting the usefulness of CXR as a diagnostic tool. In 2010–11, the Zambian Prison Service and Ministry of Health established TB and HIV screening programs in six prisons; screening included digital radiography for all participants. Using front-line clinicians we evaluated sensitivity, specificity and inter-rater agreement for digital CXR interpretation using the Chest Radiograph Reading and Recording System (CRRS). Digital radiographs were selected from HIV-infected and uninfected inmates who participated in a TB and HIV screening program at two Zambian prisons. Two medical officers (MOs) and two clinical officers (COs) independently interpreted all CXRs. We calculated sensitivity and specificity of CXR interpretations compared to culture as the gold standard and evaluated inter-rater reliability using percent agreement and kappa coefficients. 571 CXRs were included in analyses. Sensitivity of the interpretation "any abnormality" ranged from 50–70 % depending on the reader and the patients' HIV status. In general, MO's had higher specificities than COs. Kappa coefficients for the ratings of "abnormalities consistent with TB" and "any abnormality" showed good agreement between MOs on HIV-uninfected CXRs and moderate agreement on HIV-infected CXRs whereas the COs demonstrated fair agreement in both categories, regardless of HIV status. Sensitivity, specificity and inter-rater agreement varied substantially between readers with different experience and training, however the medical officers who underwent formal CRRS training had more consistent interpretations.

The World Health Organization recommends the roll-out of light-emitting diode (LED) fluorescent microscopes (FM) as an alternative to light microscopes in resource-limited settings. We evaluated the acceptability and performance of three LED FMs after a short orientation among laboratory technicians from government health centers in Zambia. Sixteen technicians with varied light microscopy experience were oriented to FMs and divided into groups; each group read a different set of 40 slides on each LED FM (Primo Star iLED™, Lumin™, FluoLED™) and on a reference mercury-vapor FM (Olympus BX41TF). Slide reading times were recorded. An experienced FM technician examined each slide on the Olympus BX41TF. Sensitivity and specificity compared to TB culture were calculated. Misclassification compared to the experienced technician and inter-rater reliability between trainees was assessed. Trainees rated microscopes on technical aspects. Primo Star iLED™, FluoLED™ and Olympus BX41TF had comparable sensitivities (67%, 65% and 65% respectively), with the Lumin™ significantly worse (56%; p<0.05). Specificity was low for trainees on all microscopes (75.9%) compared to the experienced technician on Olympus BX41TF (100%). Primo Star iLED™ had significantly less misclassification (21.1% p<0.05) than FluoLED™ (26.5%) and Lumin™ (26.8%) and significantly higher inter-rater reliability (0.611; p<0.05), compared to FluoLED™ (0.523) and Lumin™ (0.492). Slide reading times for LED FMs were slower than the reference, but not significantly different from each other. Primo Star iLED™ rated highest in acceptability measures, followed by FluoLED™ then Lumin™. Primo Star iLED™ was consistently better than FluoLED™ and Lumin™, and performed comparably to the Olympus BX41TF in all analyses, except reading times. The Lumin™ compared least favorably and was thought unacceptable for use. Specificity and inter-rater reliability were low for all microscopes suggesting that a brief orientation was insufficient in this setting. These results provide important data for resource-limited settings to consider as they scale-up LED FMs.

Human movement affects malaria epidemiology at multiple geographical levels; however, few studies measure the role of human movement in the Amazon Region due to the challenging conditions and cost of movement tracking technologies. We developed an open-source low-cost 3D printable GPS-tracker and used this technology in a cohort study to characterize the role of human population movement in malaria epidemiology in a rural riverine village in the Peruvian Amazon. In this pilot study of 20 participants (mean age = 40 years old), 45,980 GPS coordinates were recorded over 1 month. Characteristic movement patterns were observed relative to the infection status and occupation of the participants. Applying two analytical animal movement ecology methods, utilization distributions (UDs) and integrated step selection functions (iSSF), we showed contrasting environmental selection and space use patterns according to infection status. These data suggested an important role of human movement in the epidemiology of malaria in the Peruvian Amazon due to high connectivity between villages of the same riverine network, suggesting limitations of current community-based control strategies. We additionally demonstrate the utility of this low-cost technology with movement ecology analysis to characterize human movement in resource-poor environments.

Purpose of review To advance a re-conceptualized prevention, treatment, and care continuum (PTCC) for HIV-associated tuberculosis (TB) in prisons, and to make recommendations for strengthening prison health systems and reducing HIV-associated TB morbidity and mortality throughout the cycle of pretrial detention, incarceration, and release. Recent findings Despite evidence of increased HIV-associated TB burden in prisons compared to the general population, prisoners face entrenched barriers to accessing anti-TB therapy, antiretroviral therapy, and evidence-based HIV and TB prevention. New approaches, suitable for the complexities of healthcare delivery in prisons, have emerged that may address these barriers, and include: novel TB diagnostics, universal test and treat for HIV, medication-assisted treatment for opioid dependence, comprehensive transitional case management, and peer navigation, among others. Summary Realizing ambitious international HIV and TB targets in prisons will only be possible by first addressing the root causes of the TB/HIV syndemic, which are deeply intertwined with human rights violations and weaknesses in prison health systems, and, second, fundamentally re-organizing HIV and TB services around a coordinated PTCC. Taking these steps can help ensure universal access to comprehensive, good-quality, free and voluntary TB/HIV prevention, treatment, and care, and advance efforts to strengthen health resourcing, staffing, information management, and primary care access within prisons.

From 2013, the Zambian Corrections Service (ZCS) worked with partners to strengthen prison health systems and services. One component of that work led to the establishment of facility-based Prison Health Committees (PrHCs) comprising of both inmates and officers. We present findings from a nested evaluation of the impact of eight PrHCs 18 months after programme initiation.In-depth-interviews were conducted with 11 government ministry and Zambia Corrections Service officials and 6 facility managers. Sixteen focus group discussions were convened separately with PrHC members (21 females and 51 males) and non-members (23 females and 46 males) in 8 facilities. Memos were generated from participant observation in workshops and meetings preceding and after implementation. We sought evidence of PrHC impact, refined with reference to Joshi's three domains of impact for social accountability interventions - state (represented by facility-based prison officials), society (represented here by inmates), and state-society relations (represented by inmate-prison official relations). Further analysis considered how project outcomes influenced structural dimensions of power, ability and justice relating to accountability.Data pointed to a compelling series of short- and mid-term outcomes, with positive impact on access to, and provision of, health services across most facilities. Inmates (members and non-members) reported being empowered via a combination of improved health literacy and committee members' newly-given authority to seek official redress for complaints and concerns. Inmates and officers described committees as improving inmate-officer relations by providing a forum for information exchange and shared decision making. Contributing factors included more consistent inmate-officer communications through committee meetings, which in turn enhanced trust and co-production of solutions to health problems. Nonetheless, long-term sustainability of accountability impacts may be undermined by permanently skewed power relations, high rates of inmate (and thus committee member) turnover, variable commitment from some officers in-charge, and the anticipated need for more oversight and resources to maintain members' skills and morale.Our study shows that PrHCs do have potential to facilitate improved social accountability in both state and societal domains and at their intersection, for an extremely vulnerable population. However, sustained and meaningful change will depend on a longer-term strategy that integrates structural reform and is delivered through meaningful cross-sectoral partnership.

In 2013, the Zambian Correctional Service (ZCS) partnered with the Centre for Infectious Disease Research in Zambia on the Zambian Prisons Health System Strengthening project, seeking to tackle structural, organisational and cultural weaknesses within the prison health system. We present findings from a nested evaluation of the project impact on high, mid-level and facility-level health governance and health service arrangements in the Zambian Correctional Service.Mixed methods were used, including document review, indepth interviews with ministry (11) and prison facility (6) officials, focus group discussions (12) with male and female inmates in six of the eleven intervention prisons, and participant observation during project workshops and meetings. Ethical clearance and verbal informed consent were obtained for all activities. Analysis incorporated deductive and iterative inductive coding.Outcomes: Improved knowledge of the prison health system strengthened political and bureaucratic will to materially address prison health needs. This found expression in a tripartite Memorandum of Understanding between the Ministry of Home Affairs, Ministry of Health (MOH) and Ministry of Community Development, and in the appointment of a permanent liaison between MOH and ZCS. Capacity-building workshops for ZCS Command resulted in strengthened health planning and management outcomes, including doubling ZCS health professional workforce (from 37 to78 between 2014 and 2016), new preservice basic health training for incoming ZCS officers and formation of facility-based prison health committees with a mandate for health promotion and protection. Mechanisms: continuous and facilitated communication among major stakeholders and the emergence of interorganisational trust were critical. Enabling contextual factors included a permissive political environment, a shift within ZCS from a 'punitive' to 'correctional' organisational culture, and prevailing political and public health concerns about the spread of HIV and tuberculosis.While not a panacea, findings demonstrate that a 'systems' approach to seemingly intractable prison health system problems yielded a number of short-term tactical and long-term strategic improvements in the Zambian setting. Context-sensitive application of such an approach to other settings may yield positive outcomes.

Melioidosis is an infection caused by Burkholderia pseudomallei. Most cases occur in Southeast Asia and northern Australia; <100 cases have been reported in the Americas. We conducted a retrospective study and identified 12 melioidosis cases in Panama during 2007-2017, suggesting possible endemicity and increased need for surveillance.

The impact of human population movement (HPM) on the epidemiology of vector-borne diseases, such as malaria, has been described. However, there are limited data on the use of new technologies for the study of HPM in endemic areas with difficult access such as the Amazon. In this study conducted in rural Peruvian Amazon, we used self-reported travel surveys and GPS trackers coupled with a Bayesian spatial model to quantify the role of HPM on malaria risk. By using a densely sampled population cohort, this study highlighted the elevated malaria transmission in a riverine community of the Peruvian Amazon. We also found that the high connectivity between Amazon communities for reasons such as work, trading or family plausibly sustains such transmission levels. Finally, by using multiple human mobility metrics including GPS trackers, and adapted causal inference methods we identified for the first time the effect of human mobility patterns on malaria risk in rural Peruvian Amazon. This study provides evidence of the causal effect of HPM on malaria that may help to adapt current malaria control programmes in the Amazon.

Leptospirosis represents a public health problem in Panama, with an incidence rate of 1 in 100,000 inhabitants in 2014. Despite active surveillance and reports of outbreaks in the news, publications about human leptospirosis in Panama are scarce. The objective of this study was to describe the epidemiological and clinical features of leptospirosis in a cohort of patients admitted to the national reference hospital from January 2013 to December 2018. A total of 188 patients with suspected leptospirosis were identified, but only 56.9% (107 of 188) of the medical records could be retrieved. Microagglutination assays were completed in 45% (48 of 107) of the patients, confirming leptospirosis in 29.2% (14 of 48) of the patients. The most prevalent serogroup identified was Leptospira interrogans icterohemorrhagiae (4 of 14, 28.6%). The majority of patients with confirmed disease were middle-aged (36.4 ± 15.7 years), male (11 of 14, 78.6%), and symptomatic for 6.8 ± 0.7 days before admission. The predominant clinical presentation was fever (13 of 14, 92.9%), abdominal pain (7 of 14, 50%), and jaundice (8 of 14, 57.1%). Respiratory failure (8 of 14, 57.1%), elevated creatinine levels on admission (8 of 14, 57.1%), transfusion of blood-derived products (6 of 14, 42.9%), and required use of vasopressors (4 of 14, 28.6%) were common complications. Mortality was 28.6% (4 of 14). Empiric antibiotic therapy was initiated in almost all patients (10 of 12, 83.3%), and was appropriate in 90% (9 of 10) of them. Our study highlights the high prevalence of severe disease and reveals the diagnostic challenges concealing the true burden of leptospirosis in Panama. However, the small number of confirmed patients limits the generalization of these findings.

Multiple funding sources provide research and program implementation organizations a broader base of funding and facilitate synergy, but also entail challenges that include varying stakeholder expectations, unaligned grant cycles, and highly variable reporting requirements. Strong governance and strategic planning are essential to ensure alignment of goals and agendas. Systems to track budgets and outputs, as well as procurement and human resources are required. A major goal of funders is to transition leadership and operations to local ownership. This article details successful approaches used by the newly independent nongovernmental organization, the Centre for Infectious Disease Research in Zambia.

Once thought impossible, the dedication and efforts of countless international organizations and individuals have made HIV/AIDS therapy available in developing nations where it is estimated 90% of global cases are present. Despite the vastly improved access to antiretroviral therapy (ART), in 2007 World Health Organization (WHO) estimates indicated only 31% of those infected in low- and middle income countries had accessed HIV/AIDS therapy [1, 2, 3]. Reduced human resources are a key barrier to the provision of HIV care in resource limited settings. Contributing factors include a limited supply of new healthcare workers coming into the workforce, inadequate human resource management systems for recruitment, deployment and retention, attrition due to HIV/AIDS, limited career and professional opportunities, and increasing rates of international migration [1, 4, 5]. In response to these shortages, and to maximize available human resources, the World Health Organization (WHO) published guidelines related to task-shifting, the strategy of moving tasks from highly qualified health workers to workers with shorter duration training needs. Alongside task-shifting, the WHO stresses the need for efforts to increase the overall number of trained healthcare workers and to establish appropriate quality assurance mechanisms to evaluate and monitor clinical outcomes.

Abstract Bioelectrical impedance analysis phase angle (BIA-PA) is a valid indicator of mortality risk in people living with HIV; however, it is not known whether BIA-PA is valid for people living with HIV who are overweight or obese. We assessed whether BIA-PA differentially predicted mortality by body mass index category in participants receiving clinical care at a single site between 2000 and 2012. Change in BIA-PA from the highest versus last available phase angle was assessed using multivariate logistic regression models. Eight hundred ninety participants were included in the final analyses, with 102 deaths recorded during the study period. Decline in BIA-PA was associated with mortality in underweight and normal weight participants but not in overweight or obese participants. Additional investigation is warranted to determine the appropriate clinical BIA-PA equations and parameters to identify overweight and obese patients with increased mortality risk.

Abstract Background Prevalence of gonorrhea, chlamydia and syphilis is unknown among people living with HIV (PLHIV) in Panama. Owing to the asymptomatic course and syndromic management of these infections, etiological diagnosis and epidemiological surveillance are often missed. The aim of the study was to determine the prevalence of Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and syphilis in HIV positive men, that receive care in the Infectious Diseases Clinic at Hospital Santo Tomás. Methods A cross-sectional study was conducted among male PLHIV who attended the antiretroviral therapy clinic for a routine clinical care during March and April 2022. Written consent was obtained from all participants. Blood samples were taken for syphilis screening using a rapid lateral flow test and consecutive RPR on all positive samples. First flow urine, as well as provider-collected oropharyngeal and participant-collected anal swabs were taken from the patients for PCR CT/NG testing. Statistical analysis was carried out using SPSS version 22.0 software. Chi-square test and odds ratio were done at 95% CI using significance level of p &amp;lt; 0.05. Results A total of 221 male PLHIV were included. The prevalence of CT/NG at any anatomical site was 20.3%, 13.5% for CT and 9.0% for NG. The anatomical site with the highest prevalence was the rectal site, with a prevalence of 12.2% for CT/NG. Neisseria gonorrhoeae had a prevalence of 5.4% in oropharyngeal samples. An antibody syphilis test was positive in 51.1% of the patients. Logistic regression analysis revealed that men that reported to have had sex with another male in the past year was a risk factor for CT/NG positivity at any site(AOR = 4.95, 95% CI 1.46-16.76, p 0.004). Overall, 91.4 % of the patients had good acceptance for auto collection of the rectal sample among the study group. Conclusion There is a high prevalence of CT/NG, especially at the rectum site, and high prevalence of syphilis among HIV male atients in the antiretroviral clinic at the Santo Tomás Hospital in Panama. Most individuals with an STI w tested for, reported to be asymptomatic for these infections. Public health strategies need to be implemented to increase the screening and appropiate treatment with this population. Disclosures All Authors: No reported disclosures

Peri-urban health facilities providing HIV and TB care in Zambia.To evaluate 1) the impact of Xpert® MTB/RIF on time-to-diagnosis, treatment initiation, and outcomes among adult people living with HIV (PLHIV) on antiretroviral therapy (ART); and 2) the diagnostic performance of Xpert and Determine™ TB-LAM Ag assays.Quasi-experimental study design with the first cohort evaluated per standard-of-care (SOC; first sputum tested using smear microscopy) and the second cohort per an algorithm using Xpert as initial test (intervention phase; IP). Xpert testing was provided onsite in Chongwe District, while samples were transported 5-10 km in Kafue District. TB was confirmed using mycobacterial culture.Among 1350 PLHIV enrolled, 156 (15.4%) had confirmed TB. Time from TB evaluation to diagnosis (P = 0.018), and from evaluation to treatment initiation (P = 0.03) was significantly shorter for IP than for SOC. There was no difference in all-cause mortality (7.0% vs. 8.6%). TB-LAM Ag showed higher sensitivity with lower CD4 cell count: 81.8% at CD4 < 50 cells/mm3 vs. 31.7% overall.Xpert improved time to diagnosis and treatment initiation, but there was no difference in all-cause mortality. High sensitivity of Determine TB-LAM Ag at lower CD4 count supports increased use in settings providing care to PLHIV, particularly with advanced HIV disease.Structures de santé péri urbaines offrant des soins VIH et TB en Zambie.Evaluer 1) l’impact du Xpert® MTB/RIF sur le délai de diagnostic, de mise en route du traitement et les résultats chez des PLVIH adultes (personnes vivant avec le VIH) sous traitement antirétroviral (TAR) ; et 2) la performance diagnostique des test Xpert et Determine™ TB-LAM Ag.Ceci était une étude quasi-expérimentale dont la première cohorte a été évaluée par normes de soins (standard of care [SOC], c’est-à-dire premier crachat testé par microscopie de crachats) et la deuxième cohorte, par un algorithme basé sur l’Xpert comme test initial (phase d’intervention [IP]) L’Xpert était sur place dans le district de Chongwe, tandis que les échantillons ont été transportés à 5–10 km dans le district de Kafue. La TB a été confirmée par culture de mycobactéries.Parmi 1350 PLVIH enrôlés, 156 (15,4%) ont eu une confirmation de TB. Le délai entre l’évaluation de la TB et le diagnostic (P = 0,018) et entre l’évaluation et la mise en route du traitement (P = 0,03) a été significativement plus court pour IP comparé à SOC. Il n’y a pas eu de différence en termes de mortalité de toutes causes (7,0% contre 8,6%). Determine TB-LAM a montré une sensibilité plus élevée avec un nombre de CD4 plus faible : 81,8% avec CD4 < 50 cellules/mm3 contre 31,7% dans l’ensemble.L’Xpert a amélioré le délai de diagnostic et d’initiation du traitement, mais il n’y a pas eu de différence en termes de mortalité de toutes causes. La sensibilité élevée de Determine TB-LAM à des nombres de CD4 plus faibles est en faveur d’une utilisation accrue dans les contextes offrant des soins aux PLVIH, particulièrement en cas de maladie à VIH avancée.Centros periurbanos que prestan servicios contra la infección por el VIH y la TB en Zambia.Evaluar: 1) el impacto de la prueba Xpert® MTB/RIF sobre el lapso hasta el diagnóstico y hasta el comienzo del tratamiento y sobre los desenlaces en adultos con infección por el VIH (PLVIH) que reciben tratamiento antirretrovírico (TAR); y 2) el rendimiento diagnóstico de las pruebas Xpert and Determine™ TB-LAM Ag.Fue este un estudio semiexperimental con una primera cohorte evaluada según las normas de referencia (SOC, examen de la primera muestra de esputo mediante microscopia) y la segunda cohorte, siguiendo un algoritmo con la prueba Xpert como examen inicial (IP, fase de intervención). La prueba Xpert se realizó localmente en el Distrito Chongwe y en el Distrito Kafue las muestras se trasportaron de 5–10 km. La confirmación de la TB se obtuvo mediante el cultivo de micobaterias.De las 1350 PLVIH inscritas, en 156 (15,4%) se confirmó la TB. El lapso entre la evaluación por TB y el diagnóstico (P = 0,018) y entre la evaluación y el comienzo del tratamiento (P = 0,03) fue significativamente más corto en el grupo IP que en el grupo SOC. No se observó ninguna diferencia con respecto a la mortalidad por todas las causas (7,0% contra 8,6%). La prueba Determine TB-LAM ofreció una sensibilidad más alta cuando la cifra de linfocitos CD4 era más baja: 81,8% con < 50 células CD4/mm3, contra 31,7% en general.La prueba Xpert mejoró el lapso hasta el diagnóstico y el comienzo del tratamiento, pero no modificó la mortalidad por todas las causas. La sensibilidad alta de la prueba Determine TB-LAM con una cifra inferior de linfocitos CD4 respalda el incremento de su utilización en los entornos que prestan atención a las PLVIH, en especial en los casos de enfermedad avanzada por el VIH.

Background: Zambia is a high burden country for both human immunodeficiency virus (HIV) and tuberculosis (TB) infection and HIV clinic enrollees are a high-risk group for active TB. The advent of low-cost rapid-diagnostic technologies for TB, such as the Gene Xpert MTB/RIF assay and microscopic-observation drug-susceptibility (MODS) culture, suggest an affordable and promising diagnostic method to quickly identify and treat cases, but the cost-effectiveness of these tests are not well-established in high burden areas with a high prevalence of HIV. Methods: The objective of this study was to determine the cost-effectiveness of different TB diagnostic strategies in a cohort of HIV-infected patients in Lusaka. A cost-effectiveness analysis (CEA) was carried out using decision analysis modeling. Using the cohort proportions of HIV clinic enrollees at the Centre for Infectious Disease Research in Zambia (CIDRZ), the analysis compared the following strategies: standard of care TB diagnosis (a combination of symptom screening, sputum smear microscopy, and chest x-ray in a diagnostic algorithm), enhanced TB screening (symptom screening, sputum smear microscopy, chest x-ray and TB culture), Gene Xpert MTB/RIF Assay, MODS, and empiric treatment. Outcomes analyzed were number of cases of active pulmonary TB diagnosed and incremental cost-effectiveness ratios (ICERS). Results: Preliminary results from the base case analysis found that the standard of care was US$75.74 per case of TB detected, US$327.80 per case detected using enhanced screening, US$108.90 per case detected using Xpert, and US$41.74 per case detected using MODS. The ICERS ranged from US$34.00 per case averted using MODS or Xpert to US$252.00 per case averted using enhanced screening, where the standard of care was the comparison group. Conclusion: The decision analysis model suggests that using rapid diagnostics, particularly MODS, is very cost-effective for diagnosing TB in HIV clinic enrollees in Lusaka, Zambia.

<h3>Background</h3> Tuberculosis (TB) mortality in HIV-infected patients remains high in sub-Saharan Africa. Inadequate diagnostic tools delay time to TB treatment. <h3>Methods</h3> A two-phase TB diagnostic study was conducted among HIV-infected adult patients from 2014–2016. Patients underwent history/physical exam, chest x-ray, urine for lipoarabinomannan (LAM), sputum smear and culture. We evaluated sensitivity, specificity and time to appropriate treatment within 14 and 28 days of screening for culture-positive patients, comparing Xpert MTB/RIF assay (GXP), and LAM to standard-of-care (SOC) in 3 peri-urban clinics. chi-square and Wilcoxon Rank-Sum tests were used to test for differences between SOC and GXP for categorical variables and continuous variables, respectively. <h3>Results</h3> 1353 patients were enrolled; 755 in the SOC arm and 598 in the GXP arm. Median age was 34.3 and 65.1% were male. TB was diagnosed by any method (smear, clinical, GXP, LAM, culture) in 237 (17.5%) and with positive MTB culture in 152 (11.2%); 84 and 68 in the SOC and GXP arms, respectively. The overall sensitivity and specificity (culture as reference standard) of SOC was 91.7% and 92.9% respectively while GXP was 50.8% and 99.2%, respectively. LAM, when used with SOC, did not improve sensitivity or specificity in any CD4 strata, however when used with GXP increased sensitivity from 20% to 50% at CD4&lt;50. There was a marginally significant difference (p=0.08) at 14-day TB treatment initiation between the GXP and SOC phases but no difference at 28-days. Among those initiating therapy, the median time to TB treatment initiation was shorter for the GXP arm (4 <i>vs</i>15 days). <h3>Conclusions</h3> GXP did not significantly increase the number or accuracy of TB diagnoses compared to SOC but reduced median number of days to TB treatment by 11 days. GXP and LAM when used together have the potential to rapidly identify TB in patients with advanced HIV disease.

<h3>Background</h3> In Zambia, prison health and health services are in a state of ‘chronic emergency’. Since 2013, the Zambian Corrections Service (ZCS) partnered with Centre for Infectious Disease Research in Zambia (CIDRZ) to understand and strengthen prisoner health and access to healthcare. A key component of this work was the establishment of 11 facility-level Prison Healthcare Committees (PrHCs) comprising officer and inmate members, with a specific remit to deliver health education and provide monitoring for facility level service access. Findings presented are from operations research evaluating the feasibility of these PrHCs. <h3>Methods</h3> Mixed qualitative methods included, in-depth interviews (11 Ministry and ZCS officials; 6 facility managers) and focus group discussions (FGDs) with members of 6 PrHCs, and 6 groups of non-PrHC-inmates in the same facilities. Memos were generated from participant observation in workshops and meetings preceding and after implementation. All activities were subject to verbal informed consent and interviews and FGDs were audio-recorded with permission. <h3>Results</h3> Key informants were strongly supportive of PrHCs, noting potential for improved health information dissemination, strengthened preventive service-coverage, routine service monitoring and facility-level accountability. PrHC members confirmed ZCS-led training had taken place and that they had been given authority to deliver information-based health interventions and facilitate quicker referrals to primary care. The early phase of implementation (3–6 months at data collection) produced mixed accounts regarding PrHCs9 capacity to fulfil other preventive services or conduct data collection. Departure of PrHC members due to transfer and/or release was the most frequently listed challenge. <h3>Conclusions</h3> These data suggest the feasibility of establishing a committee comprising both officers and inmates to address a fundamental gap in facility-level mechanisms for health information delivery and service accountability. Findings nonetheless suggest PrHCs will require iterative adjustments and ongoing problem-solving by local officials. Context-sensitive application of these principles to other settings may yield positive outcomes.

Abstract Background Nontuberculous mycobacteria (NTM) are becoming more frequently isolated in microbiology laboratories. There is no standardized diagnosis, treatment, and/or monitoring of patients with NTM disease. We described the experience of the Panama National Mycobacterial Laboratory in isolating NTM in patients suspected to have active tuberculosis in Panama. Methods Data registries of the National TB Program Laboratory of Panama between 2012 and 2015 were reviewed. Demographic information, relevant history, sample source, and isolate identified for each specimen obtained at the time of specimen submission was extracted. Identification of mycobacterial species were made using culture and PCR. Data were exported to an Excel workbook and a descriptive analysis was performed using STATA. Results A total of 4,545 samples were received during this period. Of these, 288 (6.3%) were not processed. From the remaining 4,257 samples, 705 (16.5%) were negative, 2,783 (65.3%) were positive for M. tuberculosis, and 769 (18%) were confirmed NTM. NTM species identification was achieved in 715 (93%) using PCR. Median age was 55 years (0 – 92); 49.4% were male. The most frequent NTM isolate was M. avium complex in 172 (22.3%) samples, followed by M. fortuitum in 131 (17%). M. chelonae was isolated in 98 (12.7%) samples, M. gordonae in 50 (6.5%), M. scrofulaceum in 20 (2.6%), and M. triviale in 16 (2.0%). NTM isolation steadily rose over the study period with 490 (63.7%) of the samples being from 2015 and 465 (94.5%) of these typified by PCR. Specimens mainly originated from the Panama metropolitan area (88.2%) and were mostly sputum samples (70.8%). Conclusion Nontuberculous mycobacteria represented an important proportion of isolates among TB suspects in Panama. The implementation of more sensitive diagnostic techniques is increasing the recovery of NTM. Further evaluation of the clinical significance of these finding is required for appropriate guideline implementation. Disclosures G. Henostroza, Aeras: Investigator, Grant recipient.

Abstract Background An effective tuberculosis (TB) vaccine is urgently needed to support the End TB Strategy to reduce the number of new TB cases by 80% by 2030. M72/AS01E candidate vaccine is an adjuvanted recombinant fusion protein derived from Mycobacterium tuberculosis Mtb32A and Mtb39A proteins. Methods We conducted a randomized, double-blind, placebo-controlled phase 2b trial (NCT01755598) in Southern and Eastern Africa to assess M72/AS01E’s efficacy against bacteriologically confirmed pulmonary TB disease in HIV-seronegative (HIV–) adults aged 18–50 years infected with Mtb (defined by a positive IFN-γ release assay). Participants were randomized 1:1 to receive M72/AS01E or placebo at day D0 and D30. Reactogenicity, safety, immunogenicity were assessed, and incident TB disease measured from D30 postdose 2 up to ≥24 months for this analysis (follow-up ongoing up to 37 months). Efficacy against various TB disease case definitions (Figure 1) was estimated. Primary objective: efficacy against culture- or PCR-confirmed pulmonary TB disease in HIV– adults (case definition 1; success criterion: lower limit of 90% 2-sided CI &amp;gt;0%, power: 80%). Results Demographic characteristics were similar between M72/AS01E (1786) and placebo (1787) recipients. Efficacy against pulmonary TB disease case definition 1 was 54.0% (90% CI: 13.9, 75.4; P = 0.042); efficacy against other case definitions and a sensitivity analysis are shown in Figure 1. Leading solicited symptoms were pain, fatigue, and headache (Figure 2). In all recipients, unsolicited symptoms (D0–29) were more frequent after M72/AS01E (67.4%) than placebo (45.4%), mainly attributable to increased injection site reactions and flu-like symptoms. Serious adverse events (D0–month 7) incidences were similar between groups (M72/AS01E: 1.6%; placebo: 1.8%). During the study, 24 adults died (14 due to traumatic events); all deaths were unrelated to the trial. Conclusion M72/AS01E presents a clinically acceptable safety profile and significantly reduces bacteriologically confirmed pulmonary TB disease incidence in HIV– adults with latent Mtb infection. Funding. BMGF; Aeras; DFID UK; DGIS; AusAID; GlaxoSmithKline Biologicals SA. Disclosures O. Van Der Meeren, GSK: Employee and Shareholder, Salary. M. Hatherill, Aeras: Investigator, Research grant. R. J. Wilkinson, GSK: Grant Investigator, indirect funding. H. M. Ayles, GSK: Grant Investigator, Research grant. G. Henostroza, Aeras: Investigator, Grant recipient. M. A. Demoitié, GSK: owns stocks and is named inventor on patent applications relating to certain uses of M72/AS01E, Salary. T. Singh, GSK: Employee and Shareholder, Salary. E. J. Akite, GSK: Employee, Salary. A. K. Azam, GSK: Employee, Salary. A. Bollaerts, GSK: Employee, Salary. A. M. Ginsberg, GSK: Collaborator, Research support. BMGF: Grant Investigator, Grant recipient. UK DFID: Grant Investigator, Grant recipient. P. Gillard, GSK: Employee and Shareholder, Salary and stock. D. R. Tait, Aeras: Employee, Salary. GSK: Shareholder, Salary.

A cohort of patients admitted from January 2013 to December 2018 to a tertiary hospital in Panama with suspected leptospirosis was retrospectively reviewed. We considered suspected cases those that had a serology test for leptospirosis requested, even if the sample was not obtained. Demographic data, clinical signs and symptoms, laboratory profile and treatment regimens were collected from medical charts. Only those patient’s whos’ medical paper records were available for review at the archives were included in the analysis. Microagglutination assay (MAT) results were used to confirm or rule out leptospirosis. This test requires obtaining paired serum or blood samples, the first one 10-12 days after onset of symptoms and the second one at least 10 days later.